Journal
CELL
Volume 184, Issue 17, Pages 4430-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2021.07.033
Keywords
-
Categories
Funding
- NIH [T32 HL069765, F31 AI145189, T32 AI007163]
- U.S. Defense Threat Reduction Agency-Joint Science and Technology Office for Chemical and Biological Defense [HDTRA1-13-1-0034]
- CTSA award from the U.S. National Center for Advancing Translational Sciences [UL1 TR000445]
- NIAID [75N93019C00073, U19 AI142790]
Ask authors/readers for more resources
Antibody responses to alphavirus E1 proteins are influenced by the exposure of epitopes on the glycoprotein and their presentation on the cell surface. Therapeutic efficacy in vivo corresponds with virus egress inhibition potency in vitro, and treatment does not require Fc-mediated effector functions.
Alphaviruses cause severe arthritogenic or encephalitic disease. The E1 structural glycoprotein is highly conserved in these viruses andmediates viral fusion with host cells. However, the role of antibody responses to the E1 protein in immunity is poorly understood. We isolated E1-specific human monoclonal antibodies (mAbs) with diverse patterns of recognition for alphaviruses (ranging from Eastern equine encephalitis virus [EEEV]-specific to alphavirus cross-reactive) from survivors of natural EEEV infection. Antibody binding patterns and epitope mapping experiments identified differences in E1 reactivity based on exposure of epitopes on the glycoprotein through pH-dependent mechanisms or presentation on the cell surface prior to virus egress. Therapeutic efficacy in vivo of these mAbs corresponded with potency of virus egress inhibition in vitro and did not require Fc-mediated effector functions for treatment against subcutaneous EEEV challenge. These studies reveal the molecular basis for broad and protective antibody responses to alphavirus E1 proteins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available